Immunology: Defence systems against disease

Ongoing research in the field of Immuno-genetics in Sri Lanka is striving to find effective treatment of severe dengue and colon cancer, two diseases with high fatality rates in the country, an international expert on Autoimmune disorders and Immunogenetics Prof.Suranjith Seneviratne said. In an interview with the Sunday Observer Prof.Seneviratne said the this speciality of medicine which is rather new to the country is being effectively used to combat cancer and other infectious diseases in the West.

The excerpts of the interview,

Q:What is immunology and why is it important?

A. There are general practitioners and organ based specialists like cardiologists, pulmonologists, dermatologists, nephrologists. Immunology and genetics go across all these specialties. For many conditions, like the kidney disease the ultimate problem would be an immune problem.

It would be similar to a defence system in a country. The immune system immediately gets activated when a harmful organism enters the body. Humans are born with a weak immune system, it matures in the first five years and for the rest of the childhood. At this stage, the immune system needs to be looked after. It provides protection against infections caused by bacteria, fungi, viruses and worms and other organisms.

In dengue and leptospirosis (rat fever), two common diseases in Sri Lanka, the immune system overacts. The immune system has to shut down once the job is done. In dengue, some of the cells and chemicals in the immune system overacts, this causes a leakage of fluid and then the people go into dengue hemorrhagic fever (DHF)and into shock.

This is another area where I use my knowledge of immunology, to work out why these occur, what is happening in dengue, why do people get dengue and why only some develop DHF. If we can identify why some people get only dengue and not develop DHF, the DHF patients can be treated better. That is where immunology comes in.

Leptospirosis too causes a lot of complications - it affects kidneys and lungs. There is a lot of research going on in this area with the Galle Group leading. In a research with the Galle group on Leptospirosis we tried to remove the immune mediators using a special procedure. It was published recently.

Q: What is immunodeficiency?

A. Immunodeficiency is the complete failure or compromise of the ability of the immune system to fight against infections. At the Sri Lanka College of Microbiologists I gave a talk on Immunodeficiency diseases. I spoke on how to recognise immunodeficiency. If the microbiologists and infection doctors recognise it early, then an immunologist can identify the problem and treat the patient.

Q: What causes immunodeficiency disorders?

A. It varies. The primary immune deficiency is mostly genetic. We are doing a lot of research in this area. Twenty years ago, we didn’t have a clue as to what causes this condition. Today, we are aware of about twenty per cent of the causes. In another twenty years we might find the next thirty per cent.

The others are secondary causes like HIV infections as well as excessive use of steroids. Patients with asthma, dermatology problems like eczema are given many steroids and as a result the immune systems can get affected. Their systems are at risk of getting infections and other conditions related to immunodeficiency.

Q: How far have you progressed in your dengue research ?

A. We have published a number of papers on dengue recently, but if you are thinking of a cure, that is still a distant dream.

Yet, we have found certain clues. I am also a member the Navaloka Education and Research Foundation and we recently published a paper, for the first time in the world, where those who can develop severe dengue can be predicted by measuring certain altered lymphocytes, which we called atypical lymphocytes. It was published this year in ‘PLOS Medicine’.

If that is an early marker then we can intervene to prevent people from developing severe dengue. The problem at the moment is that there is no known technique to identify who would develop severe dengue when patients come to hospital. We need to know that early.

That was one advancement in our study at the Navaloka Foundation. People with high atypical lymphocytes were the ones developing severe dengue, if you can put about three or four markers like that together, that would be excellent to make a correct diagnosis.

Q: Do you have any explanation as to why we haven’t been able to come up with an effective dengue drug so far?

A. The first dengue drug was a failure. The people are trying to focus on a vaccine. If there is an effective vaccine, that will be a major breakthrough in preventing dengue cases or if they get it to reduce the severity. That research is ongoing in different parts of the world.

The first vaccine which was introduced in other countries including the Philippines, was found to be causing issues and it has been withdrawn.

The other vaccines are on trial in many countries.

There are patterns of dengue, if you know what these patterns are, which organs are involved, what age is affected, what area is affected ,then you know where to utilise the resources to get optimal results.

Dr.Priyankara Jayaratne, who is a physician at the Colombo National Hospital said that at the last dengue epidemic in 2017, they formed a special dengue ward. A study found that when forming such wards a concentration of resources did help improve the outcome.

My research is trying to find why people get severe dengue, when fluid begins to leak and patients go into shock and why some people do not develop DHF. If we work that out then a certain guideline to show how we can intervene can be derived.

Severe dengue affects liver, kidneys, lungs, and other organs.This is the group we have to target,that’s where you get morbidity (complications) and mortality (death). The doctors the world over are still trying to find why it’s occurring, using immunology and immunogenetics - that is my approach to it.

Q: What is the area of your research on cancer?

A. I am doing research on colon cancer, that is about the third commonest cancer in Sri Lanka but poorly studied. When it comes to auto immune diseases it’s still a hazy concept for people.

Auto immunity is the immune system attacking the body, rather than attacking the harmful thing. There is thyroid autoimmunity, lung auto immunity. With cancer ultimately it is the same, the immunity system is not doing what it should do. If the immune system is not getting rid of the cells that are bad, you start getting a cancer.

A lot of people look at data in the West and assume that what happens in the West,happens here, which is absolutely wrong. Even the patterns of food allergies are so different here than the West.

This is the reason why we are doing research in colorectal cancer, to identify this cancer and how it behaves among Sri Lankans.

We are looking to see the genetics of colon and bowel cancer. When a patient gets a condition, tests are done to find who should be given drug A or B or C. Twenty years ago, everyone was given Drug A and if it is rejected the doctors will move on to Drug B, etc.

Q: You said the reasons of developing colorectal cancer among Sri Lankans differ from patients in the West ?

A. Still, our data is preliminary to establish anything, what we have so far noted is that some changes in dietary patterns are contributing to increase cases of colon cancer.

People are getting it at a younger age. A high meat consumption is a factor but we know Sri Lankans don’t fall in this category.

But Sri Lankans eat a lot of processed food teeming with preservatives and food additives and , fast food, and frozen food.

The additives and preservatives are hidden to the consumer, not many people read the label and even those who read quickly go through the first few ingredients. Most of them don’t understand the technical terms and the additives and preservatives in numbers in the ingredients list. When the package is very nice, people get carried away. I have also observed that the fast food outlets are mushrooming. The people feel the more you eat such food you are with the ‘in crowd’. This is something the West learned to let go some years ago. We are mirroring something that happened in the West 20-30 years ago.

Q: How will your research help in the treatment of cancer in Sri Lanka?

A. Number one is we would understand a pattern. For any condition to be treated properly you have to know the pattern , like how many young people get it, how many older people get it, how many people who consume alcohol or who smoke get cancer. That way we will put it across that this is the group we need to be targeting.

That is one area of our research. Then we strive to know why Sri Lankans are getting it, is there an immune cause or a genetic cause.

The third objective is to assess the success of the treatment that is being used at the moment, because if the proper treatment is not available, you can suggest other methods, new drugs that are used in the West.

Q: How advanced is this area of medicine in the world ?

A. When I started immunology 20 years ago, immunology of cancer was a neglected area. There was hardly any knowledge so no one went into this area of study. Now, it is one of the most interesting and important areas because there are so many drugs that have come by studying the path.

Last year the Nobel Prize for Medicine and Research was won for finding a molecule for treatment of cancer. This relates to immunotherapy. Today, cancer immunology and cancer genetics have gained momentum. Today, there is immunogenetics.

I read recently in the papers that a child had collapsed and died while playing. His brother had died the same way previously. This condition relates to genetics. If you can identify the cause then doctors can advice his family members against contact sports or to start a drug early and get screened for complications.

That is preventive or predictive testing. Such treatment is available in the West. This is an area of immunogenetics treatment we are looking to develop here. Immunogenetics spreads across a whole range of primary diseases like lung disease, kidney disease and bone disease.

Q: Other than vaccinations, is there anything that can boost our immunity?

A. I’ve told this to many people including my patients, there are interventions from outside that can work like vaccines. Vaccines are one of the biggest advances in science but there are interventions that we can do to our bodies, because our immune system needs to be looked after, just like a defence system in a country. From a young age, we must have proper sleep patterns, healthy eating patterns - eating fresh food than processed food, reducing the amount of stress, trying not to achieve over and above what we feel comfortable with and also getting out and walking are some of the things that can be recommended.

But most of the people are thinking in terms of medical interventions and vitamins. Parents come and say ‘doctor, my son’s immunity is not good, can you give him some medicine or some vitamins’. This child is not going for any sport, not sleeping properly, the child is continuously stressed out, due to back to back exams. I always tell my patients that this is always better for a normal healthy living than going for a pill or quick fixes.

Q: As an immunologist what is your take on the anti-vaccine movement in many countries since Sri Lanka has a highly successful vaccination program?

A. A vaccine produces protection against alien organisms. It gives immunological memory and when there is such attack, the immune system recognises it and makes a response immediately. By the time the immunity system makes that response on its own, some people develop complications and succumb. That is avoided by a vaccination because the system already has the whole repertoire to fight the disease. So a vaccination works like a forward defence line.

The standard vaccines have to be cheap and convenient, a mother cannot bring the child ten times for ten vaccines, then the program is bound to fail. Therefore, the vaccines are combined.

But in special circumstances like if someone is taking a lot of steroids for a medical condition, then the vaccinations can be given separately. I would absolutely support the immune programs. As an immunologist I would say follow your national schedule.

Prof. Seneviratne is an International expert in Allergic/Mast Cell disorders, Immunodeficiency, Autoimmune disorders and Immunogenetics.

He is the Director of the Centre for Mast Cell Disorders and the President of the UK-Sri Lanka Immunology Foundation, an organisation that contributes to Immunology, Allergy and Immunogeneticseducation in Sri Lanka.

He is currently at the Institute of Immunity and Transplantation, Royal Free Hospital and University College London, UK and is also a visiting professor at the Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka.